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1.
Int Endod J ; 41(12): 1072-8, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19133096

RESUMO

AIM: To test the hypothesis that extending the time of a traditional ex vivo cytotoxicity test helps to identify trends in the behaviour of root core materials and sealers, which could ultimately aid in predicting their clinical safety and performance. METHODOLOGY: Endodontic sealers and core specimens were initially tested in direct contact with L929 fibroblasts for 72 h. Cell response was estimated by measuring cellular succinate dehydrogenase activity relative to Teflon controls. Cytotoxicity (% of more active cells) was reassessed after 1, 3, 4 and 6 weeks, with the specimens stored in a physiologically balanced salt-solution between tests. RESULTS: Distinct trends in cytotoxicity among both core materials and sealers were observed over the 6-week test. Four of the six sealers and two of the three core materials showed cell viabilities of <30% of Teflon after 6 weeks (>70% cytotoxicity). CONCLUSIONS: The current results suggest that some endodontic materials have an elevated biological risk for extended intervals.


Assuntos
Materiais Restauradores do Canal Radicular/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes , Resinas Compostas/toxicidade , Dimetilpolisiloxanos/toxicidade , Combinação de Medicamentos , Resinas Epóxi/toxicidade , Fibroblastos/efeitos dos fármacos , Previsões , Guta-Percha/toxicidade , Teste de Materiais , Camundongos , Mitocôndrias/enzimologia , Poliésteres/toxicidade , Cimentos de Resina/toxicidade , Segurança , Succinato Desidrogenase/efeitos dos fármacos , Sais de Tetrazólio , Tiazóis , Fatores de Tempo , Cimento de Óxido de Zinco e Eugenol/toxicidade
2.
J Dent Res ; 97(5): 483-491, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29328868

RESUMO

For decades, dental schools in the United States have endured a significant faculty shortage. Studies have determined that the top 2 sources of dental faculty are advanced education programs and private practice. Those who have completed both DDS and PhD training are considered prime candidates for dental faculty positions. However, there is no national database to track those trainees and no evidence to indicate that they entered academia upon graduation. The objective of this study was to assess outcomes of dental school-affiliated oral sciences PhD program enrollment, graduates, and placement between 1994 and 2016. Using the American Dental Association annual survey of advanced dental education programs not accredited by the Commission on Dental Accreditation and data obtained from 22 oral sciences PhD programs, we assessed student demographics, enrollment, graduation, and placement. Based on the data provided by program directors, the average new enrollment was 33, and graduation was 26 per year. A total of 605 graduated; 39 did not complete; and 168 were still in training. Among those 605 graduates, 211 were faculty in U.S. academic institutions, and 77 were faculty in foreign institutions. Given that vacant budgeted full-time faculty positions averaged 257 per year during this period, graduates from those oral sciences PhD programs who entered academia in the United States would have filled 9 (3.6%) vacant faculty positions per year. Therefore, PhD programs have consistently generated only a small pipeline of dental school faculty. Better mentoring to retain talent in academia is necessary. Stronger support and creative funding plans are essential to sustain the PhD program. Furthermore, the oral sciences PhD program database should be established and maintained by dental professional organizations to allow assessments of training models, trends of enrollment, graduation, and placement outcomes.


Assuntos
Educação de Pós-Graduação em Odontologia/estatística & dados numéricos , Humanos , Faculdades de Odontologia/estatística & dados numéricos , Inquéritos e Questionários , Estados Unidos
3.
J Biomed Mater Res B Appl Biomater ; 83(1): 58-63, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17285613

RESUMO

Biomedical implants significantly improve the quality of life in an ever-increasing number of patients. However, inflammation of tissues around implants remains a long-term, post-placement sequelae that may contribute to implant failure. Infection-mediated failure is partly a consequence of inappropriate host response and chronic inflammation, and is mediated primarily by the secretory products of monocytes and macrophages. Although the secretion of inflammatory mediators from activated monocytes is well characterized, the resolution of mediator levels post-activation is relatively unstudied. The current study defines the time course of cytokine secretion by activated human monocytes after the activator has been removed. THP1 human monocytes were activated by LPS, and cytokine secretion was monitored over time after LPS removal using enzyme-linked immunosorbent assays (TNFalpha or IL8) or a cytokine array. The release of cytokines was compared with conditions without LPS removal. As expected, secretion of nearly all cytokines was reduced when LPS was removed, but the amount of the reduction was highly cytokine-dependent. Furthermore, levels of cytokines were stable in medium alone but not in cell-culture, suggesting an active process to either degrade or internalize secreted cytokines. Our results are consistent with clinical experience that inflammation resolves rapidly after treatment to remove bacteria or inflamed tissue. However, the differential cytokine regulation indicates a sophisticated coordination of cytokine levels probably associated with management of the wound healing response after removal of the bacterial insult. This wound healing response is one critical component of the long-term success of biomedical implants.


Assuntos
Citocinas/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Próteses e Implantes/efeitos adversos , Células Cultivadas , Citocinas/imunologia , Humanos , Inflamação/imunologia , Interleucina-8/imunologia , Lipopolissacarídeos/imunologia , Monócitos/citologia , Fator de Necrose Tumoral alfa/metabolismo
4.
J Biomed Mater Res B Appl Biomater ; 83(2): 505-11, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17471514

RESUMO

UNLABELLED: Monosodium titanate (MST) particles effectively bind specific metals and are therefore promising compounds for delivery or sequestration of metals in biological contexts. Yet, the biological properties of MST are largely unexplored. Our previous study showed that the cytotoxicity of these compounds was mild, but the nature of the dose response curves suggested that residual titanates in culture may have interfered with the assay. In the current study, we assessed the importance of these artifacts, and extended our previous results using fibroblasts for biological evaluation. We also assessed the biological response to a new type of titanate (referred to as amorphous peroxo-titanate or APT) that shows more promising metal binding properties than MST. METHODS: The degree of titanate-induced interference in the MTT (mitochondrial activity assay) was estimated by means of cell-free assays with and without a final centrifugation step to remove residual titanate particulate. Cytotoxic responses to titanates were assessed by measuring succinate dehydrogenase activity (by MTT) in THP1 monocytes or L929 fibroblasts after 24-72 h exposures. Monocytic activation by APT was assessed by TNFalpha secretion (ELISA) from monocytes with or without lipopolysaccharide (LPS) activation. RESULTS: We confirmed that residual titanate particulates may alter the SDH activity assay, but that this effect is eliminated by adding a final centrifugation step to the standard MTT procedure. Addition of MST or APT at concentrations up to 100 mg/L altered succinate dehydrogenase activity by < 25% in both monocytes and fibroblasts. Fibroblasts displayed time-dependent adaptation to the MST. APT did not trigger TNFalpha secretion or modulate LPS-induced TNFalpha secretion from monocytes. CONCLUSIONS: Although further in vitro and in vivo assessment is needed, MST and APT exhibit biological properties that are promising for their use as agents to sequester or deliver metals in biological systems.


Assuntos
Materiais Biocompatíveis/toxicidade , Fibroblastos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Óxidos/toxicidade , Titânio/toxicidade , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Fibroblastos/enzimologia , Humanos , Teste de Materiais , Camundongos , Mitocôndrias/efeitos dos fármacos , Monócitos/imunologia , Óxidos/química , Succinato Desidrogenase/análise , Titânio/química , Fator de Necrose Tumoral alfa/análise
5.
J Biomed Mater Res B Appl Biomater ; 81(2): 397-402, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17022055

RESUMO

UNLABELLED: The biological response to dental restorative polymer composites is mediated by the release of unpolymerized residual monomers. Several new composite formulations claim to reduce unpolymerized residual mass. The current study assessed the cytotoxic responses to several of these new formations and compared them with more traditional formulations. Our hypothesis predicted that if these new polymerization chemistries reduce unpolymerized residual mass, the cytotoxicity of these materials also should be reduced relative to traditional formulations. METHODS: Materials (HerculiteXRV, Premise, Filtek Supreme, CeramxDuo, Hermes, and Quixfil) were tested in vitro in direct contact with Balb mouse fibroblasts, initially, then after aging in artificial saliva for 0, 1, 3, 5, or 8 weeks. The toxicity was determined by using the MTT assay to the estimate SDH activity. Knoop hardness of the materials also was measured at 0 and 8 weeks to determine whether surface breakdown of the materials in artificial saliva contributed to cytotoxic responses. RESULTS: Materials with traditional methacrylate chemistries (Herculite, Premise, Filtek Supreme) were severely (>50%) cytotoxic throughout the 8-week interval, but materials with newer chemistries or filling strategies (Hermes, CeramXDuo, and Quixfil) improved over time of aging in artificial saliva. Hermes showed the least cytotoxicity at 8 weeks, and was statistically equivalent to Teflon negative controls. Hardness of the materials was unaffected by exposure to artificial saliva. CONCLUSIONS: Newer polymerization and filling strategies for dental composites show promise for reducing the release of unpolymerized components and cytotoxicity.


Assuntos
Resinas Compostas/química , Resinas Compostas/toxicidade , Animais , Células 3T3 BALB , Técnicas In Vitro , Teste de Materiais , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Cimentos de Resina/química , Cimentos de Resina/toxicidade , Saliva
6.
J Biomed Mater Res A ; 77(3): 470-7, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16482554

RESUMO

Blue light from dental photopolymerization devices has significant biological effects on cells. These effects may alter normal cell function of tissues exposed during placement of oral restorations, but recent data suggest that some light-induced effects may also be therapeutically useful, for example in the treatment of epithelial cancers. Reactive oxygen species (ROS) appear to mediate blue light effects in cells, but the sources of ROS (intra- versus extracellular) and their respective roles in the cellular response to blue light are not known. In the current study, we tested the hypothesis that intra- and extracellular sources of blue light-generated ROS synergize to depress mitochondrial function. Normal human epidermal keratinocytes (NHEK) and oral squamous cell carcinoma (OSC2) cells were exposed to blue light (380-500 nm; 5-60 J/cm(2)) from a dental photopolymerization source (quartz-tungsten-halogen, 550 mW/cm(2)). Light was applied in cell-culture media or balanced salt solutions with or without cells present. Intracellular ROS levels were estimated using the dihydrofluorescein diacetate (DFDA) assay; extracellular ROS levels were estimated using the leucocrystal violet assay. Cell response was estimated using the MTT mitochondrial activity assay. Blue light increased intracellular ROS equally in both NHEK and OSC2. Blue light also increased ROS levels in cell-free MEM or salt solutions, and riboflavin supplements increased ROS formation. Extracellularly applied ROS rapidly (50-400 muM, <1 min) increased intracellular ROS levels, which were higher and longer-lived in NHEK than OSC2. The type of cell-culture medium significantly affected the ability of blue light to suppress cellular mitochondrial activity; the greatest suppression was observed in DMEM-containing or NHEK media. Collectively, the data support our hypothesis that intra- and extracellularly generated ROS synergize to affect cellular mitochondrial suppression of tumor cells in response to blue light. However, the identity of blue light targets that mediate these changes remain unclear. These data support additional investigations into the risks of coincident exposure of tissues to blue light during material polymerization of restorative materials, and possible therapeutic benefits.


Assuntos
Queratinócitos/metabolismo , Luz , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Succinato Desidrogenase
7.
J Biomed Mater Res B Appl Biomater ; 78(2): 296-301, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16362965

RESUMO

Monosodium titanate (MST) is an inorganic sorbent/ion exchanger developed for the removal of radionuclides from nuclear wastes. We investigated the ability of MST to bind Cd(II), Hg(II), Au(III), or the Au-organic compound auranofin to establish the utility of MST for applications in environmental decontamination or medical therapy (drug delivery). Adsorption isotherms for MST were determined at pH 7-7.5 in water or phosphate-buffered saline. The extent of metal binding was determined spectroscopically by measuring the concentrations of the metals in solution before and after contact with the MST. Cytotoxic responses to MST were assessed using THP1 monocytes and succinate dehydrogenase activity. Monocytic activation by MST was assessed by TNFalpha secretion (ELISA) with or without lipopolysaccharide (LPS) activation. MST adsorbed Cd(II), Hg(II), and Au(III) under conditions similar to those in physiological systems. MST exhibited the highest affinity for Cd(II) followed by Hg(II) and Au (III). MST (up to 100 mg/L) exhibited only minor (<25% suppression of succinate dehydrogenase) cytotoxicity and did not trigger TNFalpha secretion nor modulate LPS-induced TNFalpha secretion from monocytes. MST exhibits high affinity for biometals with no significant biological liabilities in these introductory studies. MST deserves further scrutiny as a substance with the capacity to decontaminate biological environments or deliver metals or metal compounds for therapeutic applications.


Assuntos
Auranofina/química , Sistemas de Liberação de Medicamentos , Metais Pesados/química , Monócitos , Adsorção , Auranofina/uso terapêutico , Materiais Biocompatíveis , Linhagem Celular , Descontaminação , Humanos , Troca Iônica , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/toxicidade , Teste de Materiais , Metais Pesados/uso terapêutico , Monócitos/metabolismo , Monócitos/ultraestrutura , Resíduos Radioativos , Succinato Desidrogenase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
J Biomed Mater Res A ; 74(3): 474-81, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15983993

RESUMO

The transcription factor NFkappaB plays a key role in the tissue inflammatory response. Metal ions released into tissues from biomaterials (e.g., Au, Pd, Ni, Hg) are known to alter the binding of NFkappaB proteins to DNA, thereby modulating the effect of NFkappaB on gene activation and, ultimately, the tissue response to biomaterials. Little is known about the effect of these metals on key signaling steps prior to NFkappaB-DNA binding such as transcription factor activation or nuclear translocation, yet these steps are equally important to modulation of the pathway. Oxidative stress is known to alter NFkappaB proteins and is suspected to play a role in metal-induced NFkappaB signaling modulation. Our aim in the current study was to assess the effects of sublethal levels of Ni, Hg, Pd, and Au ions on NFkappaB activation and nuclear translocation in the monocyte, which is acknowledged as an important orchestrator of the biological response to materials and the pathogenesis of chronic disease. Sublethal concentrations of Au(III), Ni(II), Hg(II), and Pd(II) were added to cultures of human THP1 monocytic cells for 72 h. In parallel cultures, lipopolysaccharide (LPS) was added for the last 30 min to activate the monocytic cells. Then cellular cytoplasmic and nuclear proteins were isolated, separated by electrophoresis, and probed for IkappaBalpha degradation (activation) and NFkappaB p65 translocation. Protein levels were digitally quantified and statistically compared. The levels of reactive oxygen species (ROS) in the monocytic cells were measured as a possible mechanism of metal-induced NFkappaB modulation. Only Au(III) activated IkappaBalpha degradation by itself. Au(III) and Pd(II) enhanced LPS-induced IkappaBalpha degradation, but Hg(II) and Ni(II) suppressed it. Au(III), Ni(II), and Pd(II) activated p65 nuclear translocation without LPS, and all but Ni(II) enhanced LPS-induced translocation. Collectively, the results suggest that these metal ions alter activation and translocation of NFkappaB, each in a unique way at unique concentrations. Furthermore, even when these metals had no overt effects on signaling by themselves, all altered activation of signaling by LPS, suggesting that the biological effects of these metals on monocytic function may only be manifest upon activation. None of the metal ions elevated levels of ROS at 72 h, indicating that ROS were probably not direct modulators of the NFkappaB activation or translocation at this late time point.


Assuntos
Metais Pesados/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/fisiologia , NF-kappa B/fisiologia , Transdução de Sinais/efeitos dos fármacos , Cátions Bivalentes , Linhagem Celular Tumoral , Ouro/fisiologia , Humanos , Proteínas I-kappa B/metabolismo , Immunoblotting , Mercúrio/fisiologia , Monócitos/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Níquel/fisiologia , Paládio/fisiologia , Fosforilação , Transporte Proteico/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia
9.
Toxicol In Vitro ; 19(3): 365-71, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15713543

RESUMO

The objective of this study was to quantify the ability of sublethal concentrations of several gold compounds to differentially modulate the monocytic secretion of key cytokines that are important in the etiology of rheumatic diseases. Human THP1 monocytic cells were exposed to the anti-rheumatic drugs auranofin (AF), gold sodium thiomalate (GSTM) or HAuCl4 (Au(III)) for 24-72 h. Succinate dehydrogenase (SDH) activity of the monocytes was used to determine sublethal concentrations. Monocytes were then exposed to sublethal concentrations of gold compounds for 72 h, and the activator lipopolysaccharide (LPS) was added (or not) to cultures for the last 6h. The secretion of IL6, IL8, IL10, and TNFalpha were measured in cell supernatants using ELISA. Cytokine secretion was compared among concentrations and gold compounds. SDH experiments established a sublethal concentration range of 0-75 microM for GSTM and Au(III) and 0-0.5 microM for AF. In cytokine experiments, none of the compounds alone activated secretion of any of the cytokines, but all differentially (50-440%, p<0.05) increased LPS-induced secretion of IL6 and IL8 over TNFalpha and IL10. In conclusion, sublethal concentrations of AF, GSTM, and Au(III) all may differentially modulate activation of monocytic cells, and this differential modulation may be important in the mechanisms of action of these compounds.


Assuntos
Antirreumáticos/toxicidade , Auranofina/toxicidade , Cloretos/toxicidade , Citocinas/metabolismo , Compostos de Ouro/toxicidade , Tiomalato Sódico de Ouro/toxicidade , Monócitos/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Monócitos/metabolismo , Succinato Desidrogenase/metabolismo
10.
J Biomed Mater Res B Appl Biomater ; 73(2): 308-14, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15803495

RESUMO

The use of hydrophilic dental monomers in dentin bonding agents has vastly improved resin-dentin bond strengths, but incomplete polymerization of these monomers and their leaching into adjacent (pulpal) oral tissues has raised concerns about their biocompatibility. The sublethal effects of these resins are virtually unknown, but their electrophilic nature led to the hypothesis that they may alter cellular oxidative stress pathways. Glutathione balance between reduced (GSH) and oxidized (GSSG) is a major mechanism by which cells maintain redox balance and was therefore the focus of the current investigation. THP-1 human monocytic cells were exposed to hydroxyethyl methacrylate (HEMA), benzoyl peroxide (BPO), camphorquinone (CQ), or triethyelene glycol dimethacrylate (TEGDMA) for 24 h at sublethal doses, then GSH and GSSG levels were measured by means of Ellman's method adapted for cell culture. The results indicate that these dental resin compounds act at least partly via oxidative stress by increasing GSH levels at sublethal concentrations. However, the GSH-GSSG ratio was relatively unaffected. Only BPO altered the GSH-GSSG ratio at 24 h, again at sublethal levels (7.5-15 micromol/L). The results support the hypothesis that resin monomers act, at least in part, via oxidative stress, and that oxidative-stress pathways should be one focus of future investigations of monomer biocompatibility.


Assuntos
Adesivos Dentinários/farmacologia , Glutationa/metabolismo , Monócitos/fisiologia , Estresse Oxidativo/fisiologia , Butionina Sulfoximina/farmacologia , Linhagem Celular , Resinas Compostas/farmacologia , Dissulfeto de Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Metacrilatos/farmacologia , Monócitos/efeitos dos fármacos , Oxirredução , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/farmacologia
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